Inter-m-phenylene-13,14-didehydro-PE1 compounds 2

ABSTRACT

This invention comprises certain analogs of the prostaglandins in which the double bond between C-13 and C-14 is replaced by a triple bond. Also provided in this invention, are novel chemical processes and novel chemical intermediates useful in the preparation of the above prostaglandin analogs. These prostaglandin analogs exhibit prostaglandin-like activity, and are accordingly useful for the same pharmacological purposes as the prostaglandins. Among these purposes are blood pressure lowering, labor induction at term, reproductive-cycle regulation, gastric antisecretory action, and the like.

The present application is a divisional application of Ser. No. 657,739,filed Feb. 13, 1976, now issued as U.S. Pat. No. 4,029,681 on June 14,1977.

The present invention relates to prostaglandin analogs for which theessential material constituting a disclosure therefor is incorporated byreference here from U.S. Pat. No. 4,029,681, issued June 14, 1977.

I claim:
 1. A prostaglandin analog of the formula: ##STR1## wherein Z₃is oxa or methylene; WHEREIN Y₁ is --C.tbd.C--;wherein g is one, two or3; Wherein m is one to 5, inclusive; Wherein M₁ is ##STR2## wherein R₅and R₆ are hydrogen or methyl, with the proviso that one of R₅ and R₆ ismethyl only when the other is hydrogen; Wherein L₁ is ##STR3## whereinR₃ and R₄ are hydrogen, methyl, or fluoro, being the same or different,with the proviso that one of R₃ and R₄ is fluoro only when the other ishydrogen or fluoro; Wherein R₁ is hydrogen, alkyl of one to 12 carbonatoms, inclusive, cycloalkyl of 3 to 10 carbon atoms, inclusive, aralkylof 7 to 12 carbon atoms, inclusive, phenyl, phenyl substituted with one,two, or three chloro or alkyl of one to 3 carbon atoms, inclusive, or apharmacologically aceptable cation.
 2. A compound according to claim 1,wherein is ##STR4##
 3. A compound according to claim 2, wherein M₁ is##STR5##
 4. A compound according to claim 3, wherein g is one.
 5. Acompound according to claim 4, wherein R₃, R₄, R₅, and R₆ are allhydrogen. 6.15-epi-3,7-Inter-m-phenylene-4,5,6-trinor-3-oxa-13,14-didehydro-8β,12α-PGE₁,methyl ester, a compound according to claim
 4. 7. A compound accordingto claim 2, wherein M₁ is ##STR6##
 8. A compound according to claim 7,wherein g is three.
 9. A compound according to claim 7, wherein g isone.
 10. A compound according to claim 9, wherein R₃ and R₄ are bothhydrogen.
 11. A compound according to claim 10, wherein R₅ is methyl.12. 3,7-Inter-m-phenylene-4,5,6-trinor-3-oxa-15-methyl-13,14-didehydro-8β,12α-PGE₁, a compound according to claim
 11. 13.3,7-Inter-m-phenylene-4,5,6-trinor-3-oxa-15-methyl-13,14-didehydro-8β,12α-PGE₁, methyl ester, a compound according to claim
 11. 14. Acompound according to claim 10, wherein R₆ is methyl. 15.3,7-Inter-m-phenylene-4,5,6-trinor-3-oxa-13,14-dide hydro-8β,12α-PGE₁,15-methyl ether, a compound according to claim
 14. 16.3,7-Inter-m-phenylene-4,5,6-trinor-3-oxa-13,14-didehydro-8β,12α-PGE₁,methyl ester, 15-methyl ether, a compound according to claim
 14. 17. Acompound according to claim 10, wherein R₅ and R₆ are both hydrogen. 18.3,7-Inter-m-phenylene-4,5,6-trinor-3-oxa-13,14-didehydro-8β,12α-PGE.sub.1,a compound according to claim
 17. 19.3,7-Inter-m-phenylene-4,5,6-trinor-3-oxa-13,14-didehydro-8β,12α-PGE₁,methyl ester, a compound according to claim
 17. 20. A compound accordingto claim 9, wherein at least one of R₃ and R₄ is methyl.
 21. A compoundaccording to claim 20, wherein R₃ and R₄ are both methyl.
 22. A compoundaccording to claim 21, wherein R₅ is methyl. 23.3,7-Inter-m-phenylene-4,5,6trinor-3-oxa-15,16,16-trimethyl-13,14-didehydro-8β,12α-PGE₁,methyl ester, a compound according to claim
 22. 24. A compound accordingto claim 21, wherein R₆ is methyl. 25.3,7-Inter-m-phenylene-4,5,6-trinor-3-oxa-16,16-dimethyl-13,14-didehydro-8β,12α-PGE₁,methyl ester, 15-methyl ether, a compound according to claim
 24. 26. Acompound according to claim 21, wherein R₅ and R₆ are both hydrogen. 27.3,7-Inter-m-phenylene-4,5,6-trinor-3-oxa-16,16-dimethyl-13,14-didehydro-8β,12α-PGE₁,a compound according to claim
 26. 28.3,7-Inter-m-phenylene-4,5,6-trinor-3-oxa-16,16-dimethyl-13,14-didehydro-8β,12α-PGE₁,methyl ester, a compound according to claim
 26. 29. A compound accordingto claim 9, wherein at least one of R₃ and R₄ is fluoro.
 30. A compoundaccording to claim 29, wherein R₃ and R₄ are both flluoro.
 31. Acompound according to claim 30, wherein R₅ is methyl. 32.3,7-Inter-m-phenylene-4,5,6-trinor-3-oxa-15-methyl-16,16-difluoro-13,14-didehydro-8β,12α-PGE₁,methyl ester, a compound according to claim
 31. 33. A compound accordingto claim 30, wherein R₆ is methyl. 34.3,7-Inter-m-phenylene-4,5,6-trinor-3-oxa-16,16-difluoro-13,14-didehydro-8β,12α-PGE₁,methyl ester, 15-methyl ether, a compound according to claim
 33. 35. Acompound according to claim 30, wherein R₅ and R₆ are both hydrogen. 36.3,7-Inter-m-phenylene-4,5,6-trinor-3-oxa-16,16-difluoro-13,14-didehydro-8β,12α-PGE₁,a compound according to claim
 35. 37.3,7-Inter-m-phenylene-4,5,6-trinor-3-oxa-16,16-difluoro-13,14-didehydro-8β,12α-PGE₁,methyl ester, a compound according to claim
 35. 38. A compound accordingto claim 1, wherein is ##STR7##
 39. A compound according to claim 38,wherein M₁ is ##STR8##
 40. A compound according to claim 39, wherein gis one.
 41. A compound according to claim 40, wherein R₃, R₄, R₅, and R₆are all hydrogen. 42.15-epi-3,7-Inter-m-phenylene-4,5,6-trinor-3-oxa-13,14-didehydro-PGE₁,methyl ester, a compound according to claim
 41. 43. A compound accordingto claim 38, wherein M₁ is ##STR9##
 44. A compound according to claim43, wherein g is three.
 45. A compound according to claim 43, wherein gis one.
 46. A compound according to claim 45, wherein R₃ and R₄ are bothhydrogen.
 47. A compound according to claim 46, wherein R₅ is methyl.48.3,7-Inter-m-phenylene-4,5,6-trinor-3-oxa-16-methyl-13,14-didehydro-PGE₁,a compound according to claim
 47. 49.3,7-Inter-m-phenylene-4,5,6-trinor-3-oxa-15-methyl-13,14-didehydro-PGE₁,methyl ester, a compound according to claim
 47. 50. A compound accordingto claim 46, wherein R₆ is methyl. 51.3,7-Inter-m-phenylene-4,5,6-trinor-3-oxa-13,14-didehydro-PGE₁, 15-methylether, a compound according to claim
 50. 52.3,7-Inter-m-phenylene-4,5,6-trinor-3-oxa-13,14 -didehydro-PGE₁, methylester, 15-methyl ether, a compound according to claim
 50. 53. A compoundacording to claim 46, wherein R₅ and R₆ are both hydrogen. 54.3,7-Inter-m-phenylene-4,5,6-trinor-3-oxa-13,14-didehydro-PGE₁, acompound according to claim
 53. 55.3,7-Inter-m-phenylene-4,5,6-trinor-3-oxa-13,14-didehydro-PGE₁, methylester, a compound according to claim
 53. 56. A compound according toclaim 45, wherein at least one of R₃ and R₄ is methyl.
 57. A compoundaccording to claim 56, wherein R₃ and R₄ are both methyl.
 58. A compoundaccording to claim 57, wherein R₅ is methyl. 59.3,7-Inter-m-phenylene-4,5,6-trinor-3-oxa-15,16,16-trimethyl-13,14-didehydro-PGE₁,methyl ester, a compound according to claim
 58. 60. A compound accordingto claim 57, wherein R₆ is methyl. 61.3,7-Inter-m-phenylene-4,5,6-trinor-3-oxa-16,16-dimethyl-13,14-didehydro-PGE₁,methyl ester, 15-methyl ether, a compound according to claim
 118. 62. Acompound according to claim 57, wherein R₅ and R₆ are both hydrogen. 63.3,7-Inter-m-phenylene-4,5,6-trinor-3-oxa-16,16-dimethyl-13,14-didehydro-PGE₁,a compound according to claim
 62. 64.3,7-Inter-m-phenylene-4,5,6-trinor-3-oxa-16,16-dimethyl-13,14-didehydro-PGE₁,methyl ester, a compound according to claim
 62. 65. A compound accordingto claim 45, wherein at least one of R₃ and R₄ is fluoro.
 66. A compoundaccording to claim 65, wherein R₃ and R₄ are both fluoro.
 67. A compoundaccording to claim 66, wherein R₅ is methyl. 68.3,7-Inter-m-phenylene-4,5,6-trinor-3-oxa-15-methyl-16,16-difluoro-13,14-didehydro-PGE₁,methyl ester, a compound according to claim
 67. 69. A compound accordingto claim 66, wherein R₆ is methyl. 70.3,7-Inter-m-phenylene-4,5,6-trinor-3-oxa-16,16-difluoro-13,14-didehydro-PGE₁,methyl ester, 15methyl ether, a compound according to claim
 69. 71. Acompound according to claim 66, wherein R₅ and R₆ are both hydrogen. 72.3,7-Inter-m-phenylene-4,5,6-trinor-3-oxa-16,16-difluoro-13,14-didehydro-PGE₁,a compound according to claim
 71. 73.3,7-Inter-m-phenylene-4,5,6-trinor-3-oxa-16,16-difluoro-13,14-didehydro-PGE₁,methyl ester, a compound according to claim 71.